A Nonlethal Young Domesticated Ferret (Mustela putorius furo) Model for Studying Pandemic Influenza Virus A/California/04/2009 (H1N1)

摘要

Recent events have heightened the need for the rapid development of vaccines directed against pandemic influenza H1N1 viruses circulating during 2009 to 2010. The current study was conducted to establish a virus challenge dose for a subsequent CA/04 vaccine efficacy study in 3-mo-old domesticated ferrets. An additional consideration in using CA/04 in ferrets is the selection of endpoints on which to base the challenge dose, given the potential nonlethality of this particular model. Four doses ranging from 10⁴ to 10⁷ TCID50 units of CA/04 per animal were administered by intranasal instillation to groups of male and female ferrets, and virus titers in nasal washes obtained 1, 3, and 5 d thereafter were determined in MDCK cells. Dosed ferrets developed clinically mild infections. Peak virus titers occurred on day 3 after instillation regardless of dose. Virus-treated ferrets had less weight gain than did untreated ferrets. In conclusion, 3-mo-old ferrets can be infected with doses as low as 10⁴ TCID50 units of CA/04, and virus titers in nasal washes and decreased body weight gain can be used to assess the course of nonlethal infection of 3-mo-old ferrets by CA/04.